Randomized Trials
Clinical Trial Update | Equal long-term health and survival from restrictive vs. standard IV fluid therapy in septic shock patients
29 Jun, 2023 | 14:01h | UTCOriginal Study: RCT: A restrictive intravenous fluid strategy does not improve outcomes in ICU patients with septic shock.
RCT | Intravitreal therapy for uveitic macular edema—ranibizumab versus methotrexate versus the dexamethasone implant
29 Jun, 2023 | 13:57h | UTCIntravitreal Therapy for Uveitic Macular Edema—Ranibizumab versus Methotrexate versus the Dexamethasone Implant – Ophthalmology (link to abstract – $ for full-text)
RCT | Acupuncture, doxylamine–pyridoxine, and their combination in nausea treatment during pregnancy
29 Jun, 2023 | 13:56h | UTCAcupuncture and Doxylamine–Pyridoxine for Nausea and Vomiting in Pregnancy: A Randomized, Controlled, 2 × 2 Factorial Trial – Annals of Internal Medicine (link to abstract – $ for full-text)
Commentary: Combo treatment eases nausea and vomiting of pregnancy – MDedge
RCT | Arthroscopic capsular shift surgery shows no significant pain or functional improvement in atraumatic shoulder instability
29 Jun, 2023 | 13:45h | UTCArthroscopic capsular shift surgery in patients with atraumatic shoulder joint instability: a randomised, placebo-controlled trial – British Journal of Sports Medicine (link to abstract – $ for full-text)
RCT | Bulevirtide reduces HDV RNA and ALT levels in chronic hepatitis D patients
28 Jun, 2023 | 13:20h | UTCSummary: This randomized phase 3 trial evaluated the efficacy of bulevirtide, an inhibitor of HDV entry into hepatocytes, in patients with chronic hepatitis D. Patients were randomized to receive either 2 mg or 10 mg of bulevirtide daily for 144 weeks, or no treatment for 48 weeks followed by 10 mg bulevirtide daily for 96 weeks. The study involved 150 patients, 49 in the 2-mg group, 50 in the 10-mg group, and 51 in the control group.
After 48 weeks of treatment, 45% and 48% of patients in the 2-mg and 10-mg groups respectively achieved the primary end point of undetectable HDV RNA level or a decrease of at least 2 log10 IU per milliliter from baseline, and normalization of ALT level. Only 2% in the control group reached the primary endpoint. ALT levels normalized in 51% and 56% of patients in the 2-mg and 10-mg groups respectively, a significant difference from the 12% normalization in the control group. Notably, loss of HBsAg did not occur by week 48 in the bulevirtide groups. No serious adverse events related to the treatment were reported, though side effects including headache, pruritus, and fatigue were more common in the bulevirtide groups.
These results demonstrate the effectiveness of bulevirtide in reducing HDV RNA and ALT levels in patients with chronic hepatitis D. However, the absence of HBsAg loss in bulevirtide groups raises questions about its long-term implications.
Article: A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Presented today at #EASLCongress: In a randomized trial, 48 weeks of treatment with bulevirtide, which inhibits hepatitis D virus entry into hepatocytes, reduced HDV RNA and alanine aminotransferase levels in patients with chronic hepatitis D. https://t.co/Q8RNZFbQlQ
— NEJM (@NEJM) June 22, 2023
Perspective | Ensuring ethical postprogression therapy for patients in randomized trial control arms
28 Jun, 2023 | 13:16h | UTC
Commentary on Twitter
Ensuring Ethical Postprogression Therapy for Patients in RCT Arms
"Patients participating in clinical trials make significant sacrifices, and in return the academic and clinical communities owe them optimal treatment after progression"@JCO_ASCO https://t.co/2dv2rky2WN pic.twitter.com/rQfRx3T4Ii
— Yakup Ergün (@dr_yakupergun) June 22, 2023
RCT | Total breast reconstruction with autologous fat transfer using an expansion device vs implants in patients with breast cancer
28 Jun, 2023 | 13:12h | UTCEffect of Total Breast Reconstruction With Autologous Fat Transfer Using an Expansion Device vs Implants on Quality of Life Among Patients With Breast Cancer: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)
See also: Visual Abstract
Author Interview: Effect of Breast Reconstruction With Autologous Fat Transfer vs Implants on Quality of Life – JAMA
RCT | Cyclophosphamide-based regimen enhances GVHD-free survival after hematopoietic stem-cell transplantation
27 Jun, 2023 | 13:54h | UTCSummary: The article details a phase 3 trial comparing the efficacy of two graft-versus-host disease (GVHD) prophylactic regimens in hematologic cancer patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). The experimental group received cyclophosphamide–tacrolimus–mycophenolate mofetil, and the standard group received tacrolimus–methotrexate. The patients, a total of 431, underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched unrelated donor.
The primary end point was GVHD-free, relapse-free survival at 1 year. Results indicated a significantly higher incidence of this outcome in the experimental group (hazard ratio, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P=0.001). At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) in the experimental group, compared to 34.9% (95% CI, 28.6 to 41.3) in the standard group.
Notably, patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall survival, disease-free survival, relapse, transplantation-related death, and engraftment did not show a substantial difference between the groups. These results suggest that cyclophosphamide–tacrolimus–mycophenolate mofetil may offer a more effective prophylaxis against GVHD in HSCT patients.
Article: Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant – Johns Hopkins Medicine
Commentary on Twitter
In this trial, 1-year GVHD-free, relapse-free survival after stem-cell transplantation was 52.7% in the cyclophosphamide–tacrolimus–mycophenolate mofetil group and 34.9% in the tacrolimus–methotrexate group. https://t.co/wCdvP1LChu
— NEJM (@NEJM) June 21, 2023
RCT | Dolutegravir is noninferior as a replacement for ritonavir-boosted protease inhibitor in HIV therapy
27 Jun, 2023 | 13:52h | UTCSummary: This randomized clinical trial (RCT) assessed the switch from ritonavir-boosted protease inhibitor (PI) to dolutegravir in HIV patients without genotype information but with viral suppression. The multicenter, open-label trial, involving 795 participants across four sites in Kenya, compared those who switched to dolutegravir (398) with those continuing with their current ritonavir-boosted PI regimen (397). The primary end point was an HIV type 1 RNA level of at least 50 copies per milliliter at week 48.
At the end of the trial period, the number of patients in both groups who met the primary end point was nearly the same (5.0% in the dolutegravir group and 5.1% in the ritonavir-boosted PI group). This indicates the noninferiority of dolutegravir, within a 4% margin. Additionally, no mutations conferring resistance to either drug were detected. The incidence of treatment-related adverse events of grade 3 or 4 was similar in both groups (5.7% for dolutegravir and 6.9% for ritonavir-boosted PI).
The study concludes that dolutegravir is a noninferior alternative to ritonavir-boosted PI for previously treated, virally suppressed HIV patients lacking drug-resistance mutation data. The similar safety profiles also support the switch. However, further research may provide valuable insights on the long-term implications of the switch.
Article: Second-Line Switch to Dolutegravir for Treatment of HIV Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Second-Line Switch to Dolutegravir Noninferior in HIV – HealthDay
Commentary on Twitter
In an open-label, multicenter trial in Kenya, HIV-infected patients following a ritonavir-boosted protease inhibitor regimen were assigned to switch to dolutegravir or continue the regimen. The dolutegravir-based regimen was noninferior. https://t.co/jL70h5ejnV
— NEJM (@NEJM) June 21, 2023
RCT | Evaluating the viability of dolutegravir monotherapy in primary HIV infection
27 Jun, 2023 | 13:50h | UTCSummary: The study in focus is a randomized, controlled, non-inferiority trial spanning over 192 weeks, titled “EARLY-SIMPLIFIED”. It evaluated the effect of simplifying combination antiretroviral therapy (cART) to dolutegravir (DTG) monotherapy in patients with early-stage HIV-1 infection. The trial recruited 101 people who had begun cART within 180 days of a documented primary HIV-1 infection with suppressed viral load.
The patients were randomly divided into two groups: DTG monotherapy (n=68) and continued cART (n=33). The primary endpoints were viral failure rates at 48, 96, 144, and 192 weeks. Results revealed no difference in viral response between the two groups at 96 weeks, suggesting non-inferiority of DTG monotherapy. At the end of the trial (192 weeks), no virological failures were recorded in either group.
The study indicates that early initiation of cART during primary HIV infection might permit sustained virological suppression after switching to DTG monotherapy. However, the study was limited by its highly selected patient population and the transition to an observational design after 96 weeks. It provides insight into the potential for minimizing ART toxicity by stratifying patients according to the latent reservoir size or duration of active infection before starting therapy.
Phase 2 RCT | Orforglipron, an oral GLP-1 receptor agonist, significantly reduces weight in adults with obesity
26 Jun, 2023 | 00:58h | UTCSummary: The article reports a phase 2, randomized, double-blind trial investigating the efficacy of the GLP-1 receptor agonist, orforglipron, as an oral weight loss treatment for adults with obesity or overweight plus at least one weight-related condition. The study involved 272 participants, who were administered orforglipron at varying doses or a placebo over a 36-week period.
The key findings of the study indicated significant weight reduction in individuals who were administered orforglipron. At 26 weeks, weight changes in the orforglipron group ranged from -8.6% to -12.6% compared to -2.0% in the placebo group. At 36 weeks, these figures were -9.4% to -14.7% for the orforglipron group and -2.3% for the placebo group. Furthermore, 46-75% of orforglipron recipients experienced a weight reduction of at least 10% by week 36, compared to 9% in the placebo group.
Improvements were also observed in all prespecified weight-related and cardiometabolic measures among orforglipron users. However, the treatment was associated with some mild to moderate gastrointestinal side effects, leading to discontinuation in 10-17% of participants. The safety profile was in line with other GLP-1 receptor agonists. These findings suggest that orforglipron could potentially be an effective oral treatment for weight reduction in adults with obesity, though further research is needed to corroborate these results and assess long-term effects.
Article: Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity – New England Journal of Medicine (link to abstract – $ for full-text)
Phase 2 RCT | Oral GLP-1 agonist Orforglipron outperforms dulaglutide and placebo in type 2 diabetes control
26 Jun, 2023 | 00:54h | UTCSummary: In a 26-week, phase 2, double-blind, randomized trial spanning multiple centers in the USA, Hungary, Poland, and Slovakia, researchers examined the efficacy and safety of orforglipron, a non-peptide GLP-1 receptor agonist. The sample comprised 383 adults aged 18 and older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated hemoglobin (HbA1c) of 7.0–10.5%.
The study’s primary efficacy outcome revealed that orforglipron achieved a significantly higher mean reduction in HbA1c compared to both the placebo and dulaglutide (-2.10% vs -0.43% and -1.10%, respectively). Furthermore, orforglipron induced a change in mean body weight at week 26 of -10.1 kg, outperforming both the placebo and dulaglutide. Adverse events mostly encompassed mild to moderate gastrointestinal issues.
The study concluded that orforglipron at doses of 12 mg or higher could potentially serve as an effective alternative to injectable GLP-1 receptor agonists and oral semaglutide, for type 2 diabetes treatment. While the drug’s safety profile was consistent with other GLP-1 receptor agonists, there is a need for larger confirmatory studies and dose regimen optimization.
Article: Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study – The Lancet (link to abstract – $ for full-text)
Commentary: Orforglipron Shows Promise as Weight Loss, Diabetes Agent in Phase 2 Trials – HCP Live
Phase 2 RCT | Comparative study on CagriSema, Semaglutide, and Cagrilintide in type 2 diabetes
26 Jun, 2023 | 00:52h | UTCSummary: The study, a 32-week multicentre, randomized, double-blind, phase 2 trial, evaluated the combined effect of cagrilintide and semaglutide (CagriSema) on individuals with type 2 diabetes. 92 adults with type 2 diabetes and a BMI of 27 kg/m2 or higher were randomly assigned to one of three treatment groups: CagriSema, semaglutide, or cagrilintide.
The results indicated that the mean reduction in HbA1c was more pronounced with CagriSema than cagrilintide, but not semaglutide. The CagriSema group also showed greater weight loss versus both semaglutide and cagrilintide. In terms of safety, the most common adverse events were mild to moderate gastrointestinal events, with no fatal adverse events reported.
These findings suggest that CagriSema presents as a viable treatment option for type 2 diabetes, offering significant benefits in terms of weight loss and glycemic control. A potential limitation is the short duration of the study, which may not account for long-term effects and safety of the intervention. The authors conclude that these results support further investigation of CagriSema in larger, longer phase 3 trials.
Article: Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial – The Lancet (link to abstract – $ for full-text)
Secondary analysis of a RCT | Bempedoic acid reduces CV events in statin-intolerant patients with high CV risk
26 Jun, 2023 | 00:49h | UTCSummary: This secondary analysis of a Randomized Clinical Trial (RCT) evaluated the efficacy of bempedoic acid in primary prevention of cardiovascular events among statin-intolerant patients at high cardiovascular risk. From a total of 13,970 participants, 4206 met the criteria for primary prevention and were analyzed in this study. Those allocated to receive bempedoic acid showed a significant reduction in major cardiovascular events, reflected in a hazard ratio of 0.70.
The average age of this patient cohort was 68 years, and most participants (66%) were diagnosed with diabetes. Treatment with bempedoic acid also led to a significant 21.3% reduction in low-density lipoprotein cholesterol (LDL-C) levels and a 21.5% decrease in high-sensitivity C-reactive protein levels, suggesting improved cardiovascular health.
This study underscores the potential benefits of lipid-modulating therapy for primary prevention in high-risk patients, who are often undertreated. However, it is important to note the inherent limitations of this secondary analysis. The analysis was performed on a subgroup within a larger clinical trial, which could potentially lead to false-positive findings due to multiple testing. Furthermore, the results may not generalize to younger populations, those with lower pretreatment LDL-C levels, those without diabetes, or those with a lower baseline cardiovascular risk.
Article: Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients – JAMA (free for a limited period)
Editorial: Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease: Not a Statin Substitute but a Good Plan B – JAMA (free for a limited period)
See also: Visual Abstract
Commentary: Study Suggests Bempedoic Acid Could Find Role in Primary Prevention – HCP Live
Original Study: RCT | Bempedoic acid shows modest reduction in cardiovascular events for statin-intolerant patients
RCT | High-dose dual-antibiotic cement doesn’t lower infection rates in hip hemiarthroplasty
26 Jun, 2023 | 00:47h | UTCSummary: This randomized superiority trial studied the effect of high-dose dual-antibiotic loaded cement versus standard care single-antibiotic loaded cement on deep surgical site infection (SSI) rates in hip hemiarthroplasty patients. This large-scale study, conducted in 26 UK hospitals, included people aged 60 and older with a hip fracture.
The trial randomly allocated 4936 participants to either treatment group. The primary outcome was deep SSI at 90 days post-randomisation. Notably, no significant difference was found between the groups. About 1.7% of participants in the single-antibiotic group and 1.2% in the dual-antibiotic group experienced a deep SSI (adjusted odds ratio 1.43; 95% CI 0.87–2.35; p=0.16). This result contradicts previous findings suggesting that high-dose dual-antibiotic cement could reduce infection rates.
News release: Antibiotic bone cement found not to reduce infection after hip replacement – University of Oxford
RCT | Single-Dose VLA1553 Chikungunya vaccine shows high immunogenicity and seems safe
23 Jun, 2023 | 13:38h | UTCNews Release: First phase 3 trial of a chikungunya vaccine candidate finds it is generally safe and provokes an immune response – The Lancet
Commentary on Twitter
New: First phase 3 trial of a chikungunya vaccine candidate finds it is generally safe and provokes an immune response. https://t.co/YSzV5oxXRc pic.twitter.com/rGL7A5eLAr
— The Lancet (@TheLancet) June 13, 2023
RCT | Time-lapse-based embryo selection does not improve pregnancy rates in IVF treatments
23 Jun, 2023 | 13:37h | UTCClinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO): a three-armed, multicentre, double-blind, randomised controlled trial – The Lancet (link to abstract – $ for full-text)
News Release: New IVF Method: more expensive, not more effective – Amsterdam UMC
Commentary on Twitter (thread – click for more)
Time-lapse monitoring is increasingly used to culture and select embryos for transfer in IVF. Yet there is insufficient evidence for superior clinical results.
A study evaluated whether the embryo selection method can increase clinical results. ?https://t.co/DFqgCFHZ55
— The Lancet (@TheLancet) May 3, 2023
RCT | Dexmedetomidine administration shows promise in PTSD reduction for trauma surgery patients
23 Jun, 2023 | 13:30h | UTCSee also: Visual Abstract
RCT | Comparable 1-year outcomes for intramedullary nail vs. sliding hip screw in trochanteric fractures
22 Jun, 2023 | 15:06h | UTCInvited Commentary: A Gap Between Evidence-Based Research and Clinical Practice in Management of Hip Fractures – JAMA Network Open
Commentary on Twitter
INSITE RCT: No significant benefit to using more costly intramedullary devices over sliding hip screws for the majority of patients with trochanteric hip fractures, adding to the body of evidence that the increasing use of these implants is unwarranted. https://t.co/15iJRW5xIS
— JAMA Network Open (@JAMANetworkOpen) June 6, 2023
RCT | LMWH does not increase live birth rates in women with thrombophilia and recurrent miscarriage
21 Jun, 2023 | 13:39h | UTCHeparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial – The Lancet (link to abstract – $ for full-text)
Commentary on Twitter (thread – click for more)
New study: Many women with recurrent miscarriage are tested for inherited thrombophilia. If confirmed positive, daily subcutaneous low-molecular-weight heparin (LMWH) is given.
This is despite an absence of evidence that such treatment is beneficial ? https://t.co/0IuFhvjlZr
— The Lancet (@TheLancet) June 2, 2023
RCT | Rituximab and MMF combo improves lung function vs. MMF in interstitial lung disease with NSIP pattern, but may increase infection risk
21 Jun, 2023 | 13:16h | UTCRituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial – European Respiratory Journal (link to abstract – $ for full-text)
Commentary on Twitter
ERJ: Rituximab plus MMF is associated with benefits in lung function and progression-free survival compared with MMF plus placebo after 24 weeks of treatment. The safety profile of rituximab plus MMF was similar to that of MMF plus placebo. https://t.co/Mv0IuzLljz pic.twitter.com/1igrt6uDK4
— ERS publications (@ERSpublications) June 11, 2023
RCT | Use of lumbar drains improves 6-month outcomes in patients with aneurysmal subarachnoid hemorrhage
20 Jun, 2023 | 12:55h | UTCSee also: Visual Abstract
Commentary on Twitter
In this trial, among patients with aneurysmal subarachnoid hemorrhage, lumbar drainage improved clinical neurological outcomes at 6 months. https://t.co/SZjuQoGoku pic.twitter.com/szKcZaPL9K
— JAMA Neurology (@JAMANeuro) June 18, 2023
RCT | In chronic subdural hematoma, dexamethasone fails to match surgery for functional outcomes
20 Jun, 2023 | 12:53h | UTCDexamethasone versus Surgery for Chronic Subdural Hematoma – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Dexamethasone Compared to Burr-Hole Drainage for Chronic Subdural Hematoma – HealthDay
RCT | No superior recovery with minithoracotomy over sternotomy in mitral valve repair
20 Jun, 2023 | 12:51h | UTCMinithoracotomy vs Conventional Sternotomy for Mitral Valve Repair: A Randomized Clinical Trial – JAMA (free for a limited period)
See also: Visual Abstract
RCT | Thrice-weekly oral iron shows non-inferiority and fewer gastrointestinal effects in treating iron-deficiency anemia
20 Jun, 2023 | 12:48h | UTCA randomized controlled trial of thrice-weekly versus thrice-daily oral ferrous fumarate treatment in adult patients with iron-deficiency anemia – Ann Hematol (if the link is paywalled, try this one)